PBPK Modeling in Medaka With Bromodichloromethane (BDCM) and the Six Month Flow-Through Exposure of BDCM to Medaka
Abstract
Bromodichloromethane (BDCM) was tested at 0, 1.5, and 15 mg/L in the medaka (Oryzias latipes) model in a static exposure (<9 hours) and a flow-through exposure (six months). At the conclusion of the static exposure, fish tissue and blood were assayed for BDCM. A preliminary physiologically based pharmacokinetic (PBPK) model was built to describe the absorption, disposition, metabolism, and excretion of BDCM in medaka. Kinetic predictions from the PBPK model were linked with selected pharmacodynamic responses. Prior to BDCM dosing for the long-term exposure, half of the fish were initiated with diethylnitrosamine (DEN). After 72 hours BDCM exposure, a subset of fish were used for cell proliferation assessment. when treated fish were statistically compared to control fish, no significant cell proliferation was found, Near test termination, the 15 mg/L BDCM medaka exhibited abnormal behaviors. At test conclusion, all fish were examined histologically. Tissue changes in treated fish were statistically compared to those of control fish. Liver neoplasia was not a significant endpoint in any uninitiated treatment group. Statistically significant endpoints were found in 15 mg/L BDCM groups, regardless of DEN treatment, and included changes in the gallbladder, liver, bone, gill, kidney, and ovary.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 20, 2001
- Accession Number
- ADA397914
Entities
People
- Jason Boyd
- Jeff Fisher
- Margaret W. Toussaint
Organizations
- U.S. Army Center for Environmental Health Research